This NIH Phase I SBIR proposal aims to develop and commercialize a silicon nanowire (SiNW) sensor platform for multiplexed, label-free, biosensing applications. This single platform will provide ultrasensitive, highly specific real-time detection of a wide range of biological species by using addressable NW arrays functionalized with peptide nucleic acid (PNA) or nucleic acid aptamer capture probes. It will provide inexpensive electronic biodetection, whereas current state-of-the-art detection of biological analytes requires expensive laboratory-based equipment and highly trained specialists. In these sensors, the SiNWs act as the gate electrode in a field-effect transistor (FET) configuration and the PNA probes (genomic target) hybridize and capture complementary single-stranded DNA. The aptamer probes are generated by a selective process and immobilized, where they capture other targeted agents (e.g. proteins, toxins, cells) from solution. Captured agents at the SiNW surface generate a change in SiNW electrical conductance, allowing multiplexed detection and analysis using standard signal processing. The tunable conducting properties of semiconducting NWs combined with the ability to bind analytes on their surface makes SiNWs particularly attractive for cheap, sensitive electronic biosensor applications, and they have shown repeated success. Complementary PNA binds to DNA with great affinity and specificity, and aptamers exhibit high target affinity and exceptional specificity, allowing for detection of multiple analytes in the same reaction chamber. This exceptional binding precision enables more complete sample analyses and benefits diagnostics in, for example, oncology (protein and DNA biomarkers) and food contamination (pathogen cells and toxigenic products). PNA and aptamer immobilization chemistry is well-established, and silica (and thus SiNW) substrates are ideal for surface modification. Multiple SiNW arrays (integrated into the same circuit) will be functionalized with multiple PNA/aptamer probes, and each array will be individually addressable in hardware/software, making captured analytes easily identifiable through their matching address. Most SiNW studies have been based on a combination of "bottom-up" and "top-down" processes and have difficulties with integration, requiring delicate transfer and positioning of individual nanostructures. Other difficulties include controlling NW doping and contact resistance. This proposal will use a nanoimprint lithography (NIL) fabrication method for integrating biosensors into high-density Si circuits that excludes transporting, aligning and wiring individual SiNWs and overcomes the doping and contact resistance issues, decreasing manufacturing costs and increasing commercialization potential. Our goal in this Phase I proposal is to demonstrate the possibility of fabricating ultrasensitive, real-time, label-free, nanoscale sensors that can be economically produced and easily integrated with off-the-shelf signal processing components. We anticipate substantial commercialization opportunities and return on investment. PUBLIC HEALTH RELEVANCE: Successful commercialization of this SiNW biosensor array will allow the medical and health community to offer high-quality disease and cancer diagnostics that provide cheaper, faster and more sensitive results than all current standards. It will help guard against the spread of infectious diseases (e.g., pandemic flu), can be deployed to perform food and water safety testing, and can help arrest the propagation of antibiotic-resistant microorganisms.